A prospective, multicentre, registry study of RECO in the endovascular treatment of acute ischaemic stroke

Abstract The RECO is a novel endovascular treatment (EVT) device that adjusts the distance between two mesh segments to axially hold the thrombus. We organized this postmarket study to assess the safety and performance of RECO in acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO). This was a single-arm prospective multicentre study that enrolled patients as first-line patients treated with RECO at 9 stroke centres. The primary outcome measures included functional independence at 90 days (mRS 0–2), symptomatic intracranial haemorrhage (sICH), time from puncture to recanalization and time from symptom onset to recanalization. The secondary outcome measures were a modified thrombolysis in cerebral infarction (mTICI) score of 2b or 3 after the first attempt and at the end of the procedure and the all-cause mortality rate within 90 days. From May 22, 2020, to July 30, 2022, a total of 268 consecutive patients were enrolled in the registry. The median puncture-to-recanalization time was 64 (IQR, 45–92), and the symptom onset-to-recanalization time was 328 min (IQR, 228–469). RECO achieved successful reperfusion (mTICI 2b-3) after the first pass in 133 of 268 patients (49.6%). At the end of the operation, 96.6% of the patients reached mTICI 2b-3, and 97.4% of the patients ultimately achieved successful reperfusion. Sixteen (7.2%) patients had sICH. A total of 132 (49.3%) patients achieved functional independence at 90 days, and the all-cause mortality rate within 90 days was 17.5%. In this clinical experience, the RECO device achieved a high rate of complete recanalization with a good safety profile and favourable 90-day clinical outcomes. Clinical trial registration: URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT04840719

RETRACTED: Forensic characteristics and phylogenetic analyses of one branch of Tai‐Kadai language‐speaking Hainan Hlai (Ha Hlai) via 23 autosomal STRs included in the Huaxia™ Platinum System

Abstract Background Hainan Island, located in the South China Sea and separated from the Leizhou Peninsula by Qiongzhou Strait, is the second largest island after Taiwan in China. With the expansion of Han Chinese and the gradual formation of “South Hlai and North Han”, nowadays, Hainan Hlai is the second largest population after Han Chinese in Hainan Island. Ha Hlai, distributed in southwest and southern Hainan Island, is the dominant branch of Hlai and speaks Ha localism. Methods We utilized the Huaxia™ Platinum PCR Amplification System (including 23 autosomal STRs and 2 sex‐linked markers) to obtain the first STR profiling batch of 657 Ha Hlai individuals (497 males and 160 females). In order to explore the genetic relationships between the studied Ha Hlai and other reference populations with different language families, population genetic analyses, including PCA, MDS, STRUCTURE, and phylogenetic analysis, were conducted based upon the raw data and allelic frequencies of the polymorphic autosomal STR markers. Results In total, 271 distinct alleles were observed at the 23 STR loci. The number of diverse alleles ranged from 7 at TPOX locus to 23 at FGA locus, and the allelic frequencies varied from 0.0008 to 0.5533. In addition, the CPE and CPD were 1‐7.39 × 10−10 and 1‐3.13 × 10−28, respectively. The phylogenetic analyses indicated that Ha Hlai is a Tai‐Kadai language‐speaking and relatively isolated population which has a close genetic and geographical relationship with Hainan Hlai, and M95 is the dominant haplogroup in Ha Hlai (56.18%). Conclusion The 23 autosomal STR genetic markers were highly polymorphic as well as potentially useful for forensic applications in Hainan Ha Hlai population. The phylogenetic analyses demonstrated that small geographic scale gene flows could not be ignored and the shaping of the unique gene pool for each population was the combination effects of geographic, language, and cultural isolations

Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas

Abstract Temozolomide (TMZ) is a standard treatment for glioblastoma (GBM) patients. However, TMZ has moderate therapeutic effects due to chemoresistance of GBM cells through less clarified mechanisms. Here, we demonstrate that TMZ-derived 5-aminoimidazole-4-carboxamide (AICA) is converted to AICA ribosyl-5-phosphate (AICAR) in GBM cells. This conversion is catalyzed by hypoxanthine phosphoribosyl transferase 1 (HPRT1), which is highly expressed in human GBMs. As the bona fide activator of AMP-activated protein kinase (AMPK), TMZ-derived AICAR activates AMPK to phosphorylate threonine 52 (T52) of RRM1, the catalytic subunit of ribonucleotide reductase (RNR), leading to RNR activation and increased production of dNTPs to fuel the repairment of TMZ-induced-DNA damage. RRM1 T52A expression, genetic interruption of HPRT1-mediated AICAR production, or administration of 6-mercaptopurine (6-MP), a clinically approved inhibitor of HPRT1, blocks TMZ-induced AMPK activation and sensitizes brain tumor cells to TMZ treatment in mice. In addition, HPRT1 expression levels are positively correlated with poor prognosis in GBM patients who received TMZ treatment. These results uncover a critical bifunctional role of TMZ in GBM treatment that leads to chemoresistance. Our findings underscore the potential of combined administration of clinically available 6-MP to overcome TMZ chemoresistance and improve GBM treatment